Immune checkpoint inhibitor-associated new-onset hypophysitis: a retrospective analysis using the FAERS.

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrine Pub Date : 2024-10-01 Epub Date: 2024-07-04 DOI:10.1007/s12020-024-03949-3

Difei Lu, Jun Yao, Geheng Yuan, Ying Gao, Junqing Zhang, Xiaohui Guo

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Abstract

Background: Our study aimed to investigate the prevalence and demographic characteristics of immune checkpoint inhibitor-associated hypophysitis (ICI-hypophysitis) using data from the FAERS, and the risk factors of prognosis were explored.

Methods: In this retrospective study, all cases of newly-diagnosed hypophysitis associated with FDA approved ICIs from 1st January 2007 to 31st December 2022 were accumulated using FAERS. Demographic data including age, sex, body weight, the prognosis of cases, and other co-occurred endocrinopathies induced by ICIs were analyzed and compared between different subgroups of immunotherapy.

Results: The reporting frequency of ICI-hypophysitis was 1.46% (2343/160089). Patients on the combination therapy had higher risk of hypophysitis reporting, followed by anti-CTLA-4 agent compared with other monotherapies (p < 0.001). Male subjects displayed higher reporting risk of ICI-hypophysitis (p = 0.015). Patients on anti-PD-1 therapy or the combination therapy showed higher occurrence rate of type 1 diabetes (anti-PD-1 vs. anti-PD-L1 vs. anti-CTLA-4 vs. combination therapy, 4.2% vs. 0.7% vs. 0.3% vs. 8.4%, p < 0.001). The occurrence rate of new-onset thyroid diseases in patients receiving combination therapy was higher than anti-PD-1 monotherapy (12.3% vs. 8.4%, p = 0.010). Elder age, lung cancer, and renal cancer emerged to be positively associated with severe clinical outcomes [>65 years, OR 1.042, 95%CI (1.022-1.063), p < 0.001; lung cancer, OR 1.400, 95%CI (1.019-1.923), p = 0.038; renal cancer, OR 1.667, 95%CI (1.153-2.412), p = 0.007]. Anti-CTLA-4 monotherapy was discovered to be a protective factor of severe outcomes [OR 0.433, 95%CI (0.335-0.558), p < 0.001]. Female sex and co-occurrence of ICI-related diabetes exhibited lower risk of death [female, OR 0.571, 95%CI (0.361-0.903), p = 0.017; diabetes, OR 0.090, 95%CI (0.016-0.524), p = 0.007].

Conclusions: ICI-induced hypophysitis is male-predominant irAE, most commonly seen in patients on anti-CTLA-4 mono- or combination therapy. Awareness among clinicians is critical when patients with elder age, lung or renal cancer develop hypophysitis, which indicates poor clinical outcomes. Female sex, anti-CTLA-4 monotherapy and co-occurrence of ICI-related diabetes are protective risk factors for poor prognosis.

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与免疫检查点抑制剂相关的新发肾上腺皮质功能减退症：使用 FAERS 进行的回顾性分析。

研究背景我们的研究旨在利用FAERS的数据调查免疫检查点抑制剂相关性肾上腺皮质功能减退症（ICI-hypophysitis）的发病率和人口统计学特征，并探讨预后的风险因素：在这项回顾性研究中，利用FAERS积累了2007年1月1日至2022年12月31日期间所有新诊断的与FDA批准的ICIs相关的肾上腺皮质功能减退症病例。研究分析了人口统计学数据，包括年龄、性别、体重、病例的预后以及 ICIs 诱发的其他并发内分泌疾病，并对不同免疫治疗亚组进行了比较：结果：ICI-肾上腺皮质炎的报告频率为1.46%（2343/160089）。与其他单一疗法相比，接受联合疗法的患者报告肾上腺皮质功能减退症的风险更高，其次是抗CTLA-4药物（P 65岁，OR 1.042，95%CI (1.022-1.063)，P 结论：ICI诱发的肾上腺皮质功能减退症的发生率为1.46%（2343/160089）：ICI诱发的肾上腺皮质功能减退症是一种以男性为主的irAE，最常见于接受抗CTLA-4单药或联合治疗的患者。当高龄、肺癌或肾癌患者出现肾上腺皮质功能减退症时，临床医生的认识至关重要，因为这预示着不良的临床预后。女性、抗CTLA-4单药治疗和合并ICI相关糖尿病是预后不良的保护性风险因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.